P509 Upadacitinib improves symptomatic responses in patients with moderately to severely active Crohn’s disease

Abstract

Abstract Background Upadacitinib (UPA), an oral Janus kinase inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD), has demonstrated the ability to provide rapid symptom relief within the first week of induction treatment in patients with CD.1 As symptomatic remission is critical for patients, this phase 3 post hoc analysis evaluated the impact of UPA on patient-reported outcomes (PROs) of abdominal pain score (APS) and stool frequency (SF) over the full induction and maintenance time periods. Methods Data were pooled from the U-EXCEL (NCT03345849) and U-EXCEED (NCT03345836) induction studies evaluating patients with moderately to severely active CD with an average daily APS ≥ 2 and/or SF ≥ 4 and received UPA 45 mg (UPA45) once daily (QD) or PBO for 12 weeks. Patients who achieved clinical response to 12 weeks of UPA45 induction were re-randomised in a maintenance study (U-ENDURE, NCT03345823) to receive UPA 15 mg (UPA15) QD, UPA 30 mg (UPA30) QD, or PBO for 52 weeks. APS and SF were recorded in a daily diary and evaluated over time. Results The average daily APS (mean: PBO 1.9, UPA45 1.9) and SF (mean: PBO 5.6, UPA45 5.4), were similar between the treatment groups at induction baseline (BL). Of patients reporting BL APS ≥ 1 (PBO 91.6%, UPA45 92.4%) or BL SF ≥ 2.8 (PBO 85.6%, UPA45 85.2%), higher proportions of patients receiving UPA vs PBO achieved APS = 0 or SF ≤ 1, or complete resolution of symptoms (APS = 0 and SF ≤ 1) at week 12 of induction, as well as at week 52 of maintenance (all P ≤ .001; Figure 1A). During induction, the mean change from BL in APS and SF was improved with UPA45 vs PBO starting at week 2 through to week 12 (all P < .001; Figure 1B-C). Throughout the 52-week maintenance period, a higher proportion of patients receiving UPA15 or UPA30 achieved APS ≤ 1 or SF ≤2.8 vs PBO (Figure 1B-C). Patients treated with UPA30 demonstrated a numerically higher rate of symptomatic response vs UPA15. In patients who met the Crohn's Disease Activity Index (CDAI) criteria per US labeling (CDAI ≥ 220 at induction BL; clinical response [CR-100] at week 12 with UPA45),2 comparable symptom improvements were observed over time compared to the overall study population. Conclusion Patients with moderately to severely active CD demonstrated improvements in APS and SF as early as 2 weeks after UPA induction treatment. A greater proportion of patients achieved PRO-defined remission within 12 weeks of UPA induction treatment compared with PBO, which were sustained through week 52 of UPA maintenance treatment.